Oncolytic Gene Therapy for Prostate Cancer
Abstract
The overall purpose of this award has been to study the molecular pharmacology of replication restricted adenoviral vectors for prostate cancer gene therapy. The scope of the research is to identify relevant transcription units, which are prostate and cancer selective for the creation of potent oncolytic adenoviral vectors for ultimate translation to human clinical trials. Major findings of this award have been several. First, we have developed a first generation vector, CN706, which is prostate selective for PSA based on regulation of the ElA gene by the prostate specific enhancer promotor PSE from the PSA gene. Second, our DOD award research studies show antineoplastic action by killing by apoptosis. These vectors kill hormone refractory prostate cancer clones, which can be synergized by ionizing radiation at doses, which are clinically administered. We also have found these vectors have preclinical efficacy when given intravenously. Second, we have identified a new transcription unit, and the HIF gene as potent constructs and targets for improved gene therapy killing of hypoxic prostate cancer cells in vitro and in vivo. Our studies show that HIF is expressed as a gene therapy target in prostate cancer, but not normal prostate cells in humans and transgenic models. Basic research and creation of HIF PSA chimeric Ad S vectors has disclosed HIF is an important transcription target for oncolytic vectors. These new discoveries are currently being exploited in the creation of second generation vectors. The molecular pharmacology of oncolytic vectors suggests this is a new antineoplastic modality for hormone refractory prostate cancer.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 1999
- Accession Number
- ADA385895
Entities
People
- Jonathan W. Simons
Organizations
- Johns Hopkins University